title: Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension.
abstract: Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous abnormalities of NO synthesis and signaling have been identified in animal models of pulmonary vascular disease and in humans with pulmonary hypertension. Many of these abnormalities have become targets of new therapies for the treatment of pulmonary hypertension. However, it is unclear to what extent alterations in NO signaling contribute to pulmonary hypertensive responses or merely reflect abnormalities induced by the underlying disease. This perspective examines the current understanding of altered NO signaling in pulmonary hypertensive diseases and discusses how these alterations may contribute to the pathogenesis of pulmonary hypertension. The efficacy and limitations of presently available therapies for pulmonary hypertension that target NO signaling are reviewed along with an update on investigational therapies that use this pathway to reverse pulmonary hypertensive changes.
authors.affiliation: 1 Division of Pulmonary, Sleep, and Critical Care Medicine, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.
authors.forename: James R
authors.initials: JR
authors.lastname: Klinger
authors.forename: Steven H
authors.initials: SH
authors.lastname: Abman
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
mesh_terms: D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D065627:Familial Primary Pulmonary Hypertension; D006157:Guanosine Monophosphate / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000172:deficiency*; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; D006157:Guanosine Monophosphate